Abstract

Aim

Over the last decade we saw a dramatic improvement in treatment strategies for human epidermal growth factor receptor 2 (HER2) positive MBC. This analysis describes the observational data of MBC patients (pts) treated with trastuzumab and/or lapatinib with a special focus on type, pattern, timing of metastases and time to progression (TTP).

Methods

Information was sought from the institutional database. Clinico-pathologic factors, treatment-line and pattern of metastatic disease were collected and TTP was evaluated for each line of therapy. Cox regression model with treatment line as continuous predictor was evaluated, and a linear and a quadratic term were introduced in the model. Q test and I2-index were used to assess the presence and degree of heterogeneity across treatment lines.

Results

A total of 112 pts were reviewed. Median age was 50 (range 26–74) years (yrs), 18 pts presented metastases at initial diagnosis, 80 pts estrogen receptor positive (ER+), 57 visceral metastases and 64 pts a single metastatic site. Of note, the distribution of metastases at baseline repeated over the time, thereof visceral metastases (49%, I2 = 5%), soft tissue (41%, I2 = 0%), brain (16%, I2 = 0%), and bone (29%, I2 = 20%) data remained consistent across all lines. Patients tended to progress in the site initially affected by the disease, with an overall odds ratio (OR) of 1.9, 1.5, 1.8, and 4.2 for visceral, soft tissues, bone, and CNS disease, respectively (p < 0.0001). ER+ MBC patients resulted more likely (HR= 1.88, CI 0.97-3.64, p = 0.8I2 = 0%) to progress on bone, whereas older patients were less likely to progress on brain (HR= 0.73, CI 0.53-1.02, p = 0.07; I2 = 22%). The median number of treatment lines was 6 (range 1-17). The use of chemotherapy decreased whilst hormonotherapy increased over the time (OR = 1.10, CI= 1.04-1.17, p = 0.001). With a median follow up of 4.2 yrs, a total of 524 disease progression events were documented. Median TTP resulted superior to 4 months up to the 6th line of treatment.

Conclusions

The data suggest that MBC pts benefit from anti HER2 therapy regardless the treatment line and that risk factors for disease progression in HER2 overexpressing MBC do not significantly differ between patterns of spreading.